Label-free single and multi-photon fluorescence spectroscopy to detect brain disorders and disease: alzheimer, parkinson and autism from brain tissue, cells, spinal fluid and body fluids

Abstract

A label free single or multi-photon optical spectroscopy for measuring the differences between the levels of fluorophores from tryptophan, collagen, reduced nicotinamide adenine dinucleotide (NADH), and flavins exist in brain samples from a of Alzheimer's disease (AD) and in normal (N) brain samples with label-free fluorescence spectroscopy. Relative quantities of these molecules are shown by the spectral profiles of the AD and N brain samples at excitation wavelengths 266 nm, 300 nm, and 400 nm. The emission spectral profile levels of tryptophan and flavin were much higher in AD samples, while collagen emission levels were slightly lower and NADH levels were much lower in AD samples. These results yield a new optical method for detection of biochemical differences in animals and humans for Alzheimer's disease.

Description

BACKGROUND OF THE INVENTION1. Field of the Invention[0001]The invention generally relates to diagnostic testing of brain disorders and diseases and, more specifically to label-free one or multiple photon-emission (“PE”) such as 1 PE, 2PE and 3PE fluorescence (“PEF”) spectroscopy to detect brain disorders and diseases: Alzheimer, Parkinson and autism from brain tissue, cells, spinal fluid, and body fluids.2. Description of Prior Art[0002]Alzheimer's disease (AD), a degenerative disorder that attacks neurons in the brain and leads to the loss of proper cognition, ravages the lives of millions of people all across the world. It is the sixth leading cause of death in the United States. Although the disease has been the focus of much scientific research in past years, there still is no cure; and from 2000-2010 the proportion of deaths resulting from Alzheimer's disease in America has gone up 68%.[1] Although AD has been the focus of much scientific research in past years, there is still ...

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Benefits of technology

[0008]Optical spectroscopy has been considered a promising technique for cancer detection for more than two decades because of its advantages over the conventional diagnostic methods: no tissue removal, minimal invasiveness, less time consumption and reproducibility. Optical Biopsy was first used by Alfano et al., in 1984, who measured label free native fluorescence (NF), also called autofluorescence. Human tissue is mainly composed of an extracellular matrix of collagen fiber, proteins, fat, water, epithelial cells, which contains a number of key fingerprint native endogenous fluorophore molecules: tryptophan, collagen, elastin, reduced nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and porphyrins. Tryptophan is an amino acid required by all forms of life for protein synthesis and other important metabolic functions, accounting for the majority of protein fluorescence. NADH and FAD are involved in the oxidation of fuel molecules and can be used to probe changes in cellular metabolism. It is well known that abnormalities in metabolic activity precede the onset of many diseases: carcinoma, diabetes, atherosclerosis, brain and Alzheimer's disease. The photonic tools use fiber spectroscopic ratiometer, fiber-optic endoscope for in vivo use for detecting in situ brain disorders pumped by linear and multiphoton excitation.

Problems solved by technology

[1] Although AD has been the focus of much scientific research in past years, there is still no cure or molecular understanding.

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